Integrated Testing and Management in Fetal Growth Restriction Sifa Turan, MD, RDMS, Jena Miller, MD, and Ahmet A. Baschat, MD Growth-restricted fetuses are at higher risk for poor perinatal and long-term outcome than those who are appropriately grown. Multiple antenatal testing modalities can help docu- ment the sequence of fetal deterioration. The full extent of this compromise is best identified by a combination of fetal biometry, biophysical profile scoring, and arterial and venous Doppler. In the preterm growth-restricted fetus, timing of delivery is critically determined by the balance of fetal versus neonatal risks. In the near-term fetus, accurate diagnosis continues to be a challenge as unrecognized growth restriction contributes to a significant proportion of unexplained stillbirths. In this review, we present an integrated diagnostic and surveillance approach that accounts for these factors. Semin Perinatol 32:194-200 © 2008 Elsevier Inc. All rights reserved. KEYWORDS fetal growth restriction, non stress testing, computerized cardiotocography, bio- physical profile scoring, Doppler ultrasound, integrated testing valuation of fetal growth is common obstetric practice. havioral or cardiovascular responses to hypoxemia, but when EFetal growth restriction (FGR) affects 15% of pregnan- used in isolation may have limitations in the management of cies and is associated with significant morbidity and mortal- FGR. Integration of antenatal assessment modalities concur- ity in perinatal and adult life.1 Clinical suspicion of FGR rently evaluates physical, behavioral, and cardiovascular requires further investigation as growth delay may be the manifestations of FGR. This approach can bypass the limita- physical manifestation of many possible conditions. When tions of individual tests and therefore provide the most com- FGR is established early in pregnancy, the diagnosis is readily prehensive insight into the fetal condition to guide manage- made. In these patients, safe prolongation of pregnancy and ment. timing of delivery are critical issues. As gestational age at delivery has an independent effect on outcomes, early deliv- ery can result in neonatal complications, whereas delayed Antenatal Surveillance Tests delivery can increase stillbirth risk.2 When FGR presents in Progression of fetal hypoxemia to acidemia is an important the third trimester, clinical manifestations and signs of dete- antecendent to adverse short- and long-term outcome. rioration may be more subtle. In these patients, accurate Therefore, antenatal surveillance aims to detect fetal re- identification of FGR provides a challenge. Failure to recog- sponses that accompany such deterioration. These responses nize clinically significant FGR may contribute to over 50% of include changes in fetal heart rate pattern, dynamic variables unexplained stillbirths near term.3 (tone, movement, breathing activity), amniotic fluid volume, Antenatal surveillance modalities can provide insight into placental Doppler studies, and fetal arterial and venous many aspects of fetal well-being. Available tests are the non- Doppler parameters. stress test (NST), computerized cardiotocography (cCTG), biophysical profile score (BPS), and multi-vessel arterial and venous Doppler. Each modality independently evaluates be- Fetal Heart Rate Analysis Fetal heart rate analysis in the form of the NST is one of the first surveillance tests introduced into obstetric practice. The Department of Obstetrics, Gynecology and Reproductive Sciences, Univer- NST can be used to assess central and autonomic control of sity of Maryland, Baltimore, MD. intrinsic cardiac activity by applying visual analysis accord- Address reprint requests to Ahmet A. Baschat, MD, Department of Obstet- rics, Gynecology & Reproductive Sciences, University of Maryland, Bal- ing to criteria that have recently been updated by the Amer- 4 timore, 405 Redwood Street, Baltimore, MD 21201. E-mail: aabaschat@ican College of Obstetricians and Gynecologists. However, hotmail.com heart rate variables such as the baseline, magnitude, and du- 194 0146-0005/08/$-see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1053/j.semperi.2008.02.008 Integrated testing and management in FGR 195 ration of accelerations as well as decelerations are influenced of progressive hypoxemia and acidemia produce a predict- by many factors, including the maturational state of the fetal able effect on fetal behaviors.8 Fetal breathing movement central nervous system, gestational age, behavioral state, am- ceases first, but this may be observed over a wide pH range. niotic fluid volume, maternal status, and medications. In ad- Gross body movements and tone decrease further until they dition, there is significant intraobserver and interobserver are no longer observed over extended periods of time. Loss of variability in the interpretation of key heart rate variables, fetal tone and movement are typically observed at a median 5 even when strict interpretative guidelines are applied. Ac- pH of 7.10, and therefore provide the most consistent pre- cordingly, a “normal” reactive NST provides strong evidence diction of prelabor acidemia.11 However, when dynamic fetal of fetal well-being and absence of hypoxemia. However, a variables are considered in isolation, their predictive accu- “nonreactive” NST is a nonspecific finding, particularly in the racy for acidemia is limited by the physiologic variation that setting of FGR where delayed maturation of central fetal heart is observed in normal pregnancies.9 rate control contributes to a higher incidence of nonreactive NSTs.1 The cCTG was developed to compensate for the limita- Placental Doppler tions of visual fetal heart rate analysis. It is not widely used in the United States, but decreases inconsistencies of visual NST Doppler ultrasound of the uterine and umbilical arteries as- analysis by providing an objective interpretation of the fetal sesses the integrity of the maternal and fetal vascular com- heart rate. In addition, computer-generated variables, such as partments of the placenta. In the uterine arteries, increased the short-term variation (SVT), are derived.6 The STV ex- blood flow resistance and/or prolonged gestational persis- presses the variance in beat-to-beat intervals during a fixed tence of a diastolic notch indicates abnormal trophoblast in- time period in milliseconds. A decrease in the short-term vasion. Such suboptimal maternal placental vascularization variation below 3.5 milliseconds has been suggested as an predisposes to maternal hypertensive disorders, FGR, and optimal cutoff to identify prelabor acidemia in FGR, provid- fetal demise. In the umbilical arteries, a decline in end-dia- 7 ing superior prediction compared with the traditional NST. stolic blood flow velocities correlates with the degree of ab- An additional advantage of the cCTG is the ability to evaluate normalities in the villous vascular tree and the risk for fetal longitudinal trends of multiple fetal heart rate variables that hypoxemia, acidemia, and stillbirth.1 However, as placental cannot be assessed with the traditional NST.8 Doppler studies do not directly reflect the degree of fetal compromise, they have a limited predictive accuracy for aci- Amniotic Fluid demia and stillbirth in FGR.12 Volume Assessment Ultrasound assessment of amniotic fluid volume was added Fetal Doppler to antenatal testing to improve the prediction of poor perina- Fetal cardiovascular responses to abnormal placentation can tal outcome.9 Regulation of amniotic fluid volume is com- be observed in multiple vascular beds. From a practical plex, but by the second trimester primarily reflects fetal urine standpoint, the cerebral and precordial venous circulations production. Placental dysfunction and fetal hypoxemia may have been most widely studied in the human fetus. Increases both cause redistribution of renal blood flow leading to fetal in placental blood flow resistance and perceived fetal hypox- oliguria and consequently oligohydramnios. However, the correlation between both the four-quadrant amniotic fluid emia are associated with a decrease in the cerebroplacental index (Ͻ5 cm) or a single vertical pocket (Ͻ2 cm) with the Doppler ratio and/or increased end-diastolic velocity in the 1 actual decline in amniotic fluid volume is limited. Although cerebral circulation. These responses contribute to the pref- multiple studies have related oligohydramnios with in- erential distribution of well-oxygenated blood from the duc- creased risk for FGR, congenital abnormalities, postdates tus venosus to the brain, upper body, and the heart. With pregnancy, meconium passage, abnormal FHR patterns, and progressive placental dysfunction, abnormalities may be ob- lower Apgar scores, a reliable concordance with more objec- served in the venous flow velocity waveforms. An associated tive outcome measures such as fetal acidosis has not been decline in forward velocities during atrial systole indicates demonstrated.10 abnormalities in forward cardiac function that may be related to worsening placental disease and/or cardiac impacts of met- abolic compromise. The most severe venous Doppler abnor- Dynamic Fetal Variables malities include absence/reversal of the ductus venosus atrial Dynamic fetal variables including tone, movement, and systolic forward velocity and bi-triphasic pulsations in the breathing activity are centrally regulated components of fetal umbilical venous flow velocity profile. However, as vascu- behavior. Although these individual variables can be ob- lar